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Peer-reviewedCC BYScience Advances

Interferon-λ signaling to maternal dendritic cells protects against congenital Zika virus infection

  • Margaret R. Dedloff1
  • Thomas R. Reinhardt1
  • Tessa-Jonne F. Ropp2
  • Joel Rivera-Cardona1
  • Celeste R. Robles1
  • Rebecca L. Casazza1
  • J. Ashley Ezzell3
  • Michelle S. Itano2,4
  • Helen M. Lazear1
4 affiliations
  1. 1Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  2. 2Neuroscience Microscopy Core Facility, Carolina Institute for Developmental Disabilities & Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  3. 3Histology Research Core Facility, Department of Cell Biology & Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  4. 4Department of Cell Biology & Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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Abstract

Interferon-λ (IFN-λ, type III IFN) mediates antiviral immunity at anatomic barriers, including the maternal-fetal interface. To investigate the effects of IFN-λ during congenital Zika virus (ZIKV) infection, we infected mice lacking the IFN-αβ receptor (Ifnar1-/-) or both the IFN-αβ and IFN-λ receptors (Ifnar1-/-Ifnlr1-/-) at embryonic day 9 and found that loss of maternal IFN-λ signaling resulted in greater transplacental transmission, highlighting a protective effect of IFN-λ at the maternal-fetal interface. To investigate the spatial relationship between ZIKV infection and antiviral responses, we used HiPlex RNAscope on the entire gravid uterus and found that IFN-λ was expressed more proximal to the site of ZIKV infection in Ifnar1-/- dams compared to Ifnar1-/-Ifnlr1-/- dams. We performed immunophenotyping of the placenta and uterus by flow cytometry and found a decrease in dendritic cells and natural killer (NK) cells in the uterus of Ifnar1-/-Ifnlr1-/- dams compared to Ifnar1-/- dams, but NK cell depletion did not affect fetal infection. Using conditional knockout mice, we identified maternal dendritic cells as the key IFN-λ-responsive cell type mediating protection against ZIKV congenital infection. Together, our data support a model in which IFN-λ signaling to maternal dendritic cells increases dendritic cell accumulation in the uterus, which facilitates a protective antiviral response that restricts ZIKV congenital infection.

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Cite

BibTeXRIS
BibTeX
@article{dedloff2026interferonλ,
  title = {{Interferon-λ signaling to maternal dendritic cells protects against congenital Zika virus infection}},
  author = {Margaret R. Dedloff and Thomas R. Reinhardt and Tessa-Jonne F. Ropp and Joel Rivera-Cardona and Celeste R. Robles and Rebecca L. Casazza and J. Ashley Ezzell and Michelle S. Itano and Helen M. Lazear},
  journal = {Science Advances},
  year = {2026},
  month = oct,
  doi = {10.1126/sciadv.aeh1073},
  url = {https://www.science.org/doi/10.1126/sciadv.aeh1073},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Interferon-λ signaling to maternal dendritic cells protects against congenital Zika virus infection
AU  - Margaret R. Dedloff
AU  - Thomas R. Reinhardt
AU  - Tessa-Jonne F. Ropp
AU  - Joel Rivera-Cardona
AU  - Celeste R. Robles
AU  - Rebecca L. Casazza
AU  - J. Ashley Ezzell
AU  - Michelle S. Itano
AU  - Helen M. Lazear
PY  - 2026
DA  - 2026/10/23
JO  - Science Advances
DO  - 10.1126/sciadv.aeh1073
UR  - https://www.science.org/doi/10.1126/sciadv.aeh1073
AB  - Interferon-λ (IFN-λ, type III IFN) mediates antiviral immunity at anatomic barriers, including the maternal-fetal interface. To investigate the effects of IFN-λ during congenital Zika virus (ZIKV) infection, we infected mice lacking the IFN-αβ receptor (Ifnar1-/-) or both the IFN-αβ and IFN-λ receptors (Ifnar1-/-Ifnlr1-/-) at embryonic day 9 and found that loss of maternal IFN-λ signaling resulted in greater transplacental transmission, highlighting a protective effect of IFN-λ at the maternal-fetal interface. To investigate the spatial relationship between ZIKV infection and antiviral responses, we used HiPlex RNAscope on the entire gravid uterus and found that IFN-λ was expressed more proximal to the site of ZIKV infection in Ifnar1-/- dams compared to Ifnar1-/-Ifnlr1-/- dams. We performed immunophenotyping of the placenta and uterus by flow cytometry and found a decrease in dendritic cells and natural killer (NK) cells in the uterus of Ifnar1-/-Ifnlr1-/- dams compared to Ifnar1-/- dams, but NK cell depletion did not affect fetal infection. Using conditional knockout mice, we identified maternal dendritic cells as the key IFN-λ-responsive cell type mediating protection against ZIKV congenital infection. Together, our data support a model in which IFN-λ signaling to maternal dendritic cells increases dendritic cell accumulation in the uterus, which facilitates a protective antiviral response that restricts ZIKV congenital infection.
SN  - 2375-2548
ER  -